Reference Detail

Ref Type

Journal Article

PMID

(32461347)

Authors

Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Chen LT, Osada M, Helwig C, Dussault I, Ikeda M

Title

Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal for immunotherapy of cancer	8	1	2020 May		J Immunother Cancer

URL

Abstract Text

Patients with biliary tract cancer (BTC) have poor prognosis with few treatment options. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor (TGF)-βRII receptor (a TGF-β 'trap') fused to a human IgG1 antibody blocking programmed death ligand 1 (PD-L1), has shown clinical efficacy in multiple solid tumors.In this phase I, open-label trial expansion cohort, Asian patients with BTC whose disease progressed after first-line chemotherapy received bintrafusp alfa 1200 mg every 2 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint is safety/tolerability, while the secondary endpoints include best overall response per Response Evaluation Criteria in Solid Tumors version 1.1.As of August 24, 2018, 30 patients have received bintrafusp alfa for a median of 8.9 (IQR 5.7-32.1) weeks; 3 patients remained on treatment for >59.7 weeks. Nineteen (63%) patients experienced treatment-related adverse events (TRAEs), most commonly rash (17%), maculopapular rash and fever (13% each), and increased lipase (10%). Eleven (37%) patients had grade ≥3 TRAEs; three patients had grade 5 events (septic shock due to bacteremia, n=1; interstitial lung disease (reported term: interstitial pneumonitis), n=2). The objective response rate was 20% (95% CI 8 to 39) per independent review committee (IRC), with five of six responses ongoing (12.5+ to 14.5+ months) at data cut-off. Two additional patients with durable stable disease had a partial response per investigator. Median progression-free survival assessed by IRC and overall survival were 2.5 months (95% CI 1.3 to 5.6) and 12.7 months (95% CI 6.7 to 15.7), respectively. Clinical activity was observed irrespective of PD-L1 expression and microsatellite instability-high status.Bintrafusp alfa had clinical activity in Asian patients with pretreated BTC, with durable responses. Based on these results, bintrafusp alfa is under further investigation in patients with BTC (NCT03833661 and NCT04066491).NCT02699515.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Bintrafusp alfa	Bintrafusp alfa	0	22

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Bintrafusp alfa		MSB0011359C\|M7824	Immune Checkpoint Inhibitor 147 PD-L1/PD-1 antibody 117 TGFBR2 Antibody 3	Bintrafusp alfa is a human PD-L1 (CD274) antibody fused with transforming growth factor-beta (TGF-beta, TGFBR2) receptor II extracellular domain, which blocks two immuno-inhibitory pathways simultaneously, therefore enhances anti-tumor immunity (PMID: 29298798, PMID: 32461347).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References